Dissociation of duration-based and beat-based
auditory timing in cerebellar degeneration
Manon Grubea,1, Freya E. Coopera, Patrick F. Chinneryb,c, and Timothy D. Griffithsa,b
a
Newcastle Auditory Group, Medical School, Newcastle University, Newcastle-upon-Tyne NE2 4HH, United Kingdom; bDepartment of Neurology,
Medical School, Newcastle University, Newcastle-upon-Tyne NE2 4HH, United Kingdom; and cInstitute of Human Genetics, Newcastle University,
Newcastle-upon-Tyne NE1 3BZ, United Kingdom
Edited by William Thomas Thach, Washington University, St. Louis, MO, and accepted by the Editorial Board May 17, 2010 (received for review September
24, 2009)
This work tests the hypothesis that the cerebellum is critical to the
perception of the timing of sensory events. Auditory tasks were
used to assess two types of timing in a group of patients with a
stereotyped specific degeneration of the cerebellum: the analysis of
single time intervals requiring absolute measurements of time, and
the holistic analysis of rhythmic patterns based on relative measures
of time using an underlying regular beat. The data support a specific
role for the cerebellum only in the absolute timing of single
subsecond intervals but not in the relative timing of rhythmic
sequences with a regular beat. The findings support the existence
of a stopwatch-like cerebellar timing mechanism for absolute
intervals that is distinct from mechanisms for entrainment with
a regular beat.
human | perception | absolute | relative | subsecond
T he relevance of the human cerebellum to the perception of time
intervals and rhythmic sequences is controversial. Involvement
of the cerebellum in perceptual timing (the perception of the timing
of sensory events), in addition to its role in motor timing (the timed
execution of movements), has been suggested by a number of
studies (1–6). One distinction that we wish to address here, which
has not been made clear in previous work, is between the absolute,
duration-based timing of single subsecond intervals and the relative
timing of subsecond intervals based on a regular beat. Functional
imaging studies suggest neural activity in the human cerebellum
during the perception of the absolute duration of single time
intervals (7, 8) as well as rhythmic patterns with a regular beat (9–
13). However, previous lesion work to assess an obligatory cere-
bellar role in the perception of single time intervals has not yielded
consistent results (4, 14–17). Previous lesion work to assess any
obligatory role of the cerebellum in the analysis of rhythmic
sequences has assessed only deficits in related motor activity, such
as tapping out a beat (4, 14, 18), that do not allow clear inference
about perception.
In this study, we test whether the cerebellum is a critical sub-
strate for perceptual tasks that require the absolute, duration-
based analysis of single time intervals as well as those that require
the relative analysis of time intervals within rhythmic patterns
based on a regular beat. Perceptual tests were conducted in the
auditory domain, where accurate temporal encoding of sensory
events is essential and entrainment with a beat is induced naturally.
Tasks were administered to a group of 34 patients with a stereo-
typed cerebellar degeneration and a matched control group of 40
healthy individuals. Two absolute timing tasks tested the percep-
tion of single intervals for a variable and a fixed reference duration,
respectively (Fig. 1 A and B). Three relative timing tasks tested the
beat-based analysis of rhythmic sequences, including the detection
of the presence of a roughly regular beat (19), a deviation from an
isochronous beat (20) and a distortion of a rhythmic pattern with
a metrical beat (21) (Fig. 1 C–E). The data support a cerebellar
role in the absolute timing of single intervals, but not the relative
timing of beat-based sequences, and distinct brain mechanisms for
these two types of perceptual timing.
www.pnas.org/cgi/doi/10.1073/pnas.0910473107
Results
In all five tasks (Fig. 1), performance was measured by adaptive
tracking of thresholds (Fig. S1). Group differences (Fig. 2A)
and occurrence and severity of individual impairments were
evaluated (Figs. 2B and S2), and correlation with motor im-
pairment (Table S1) was assessed.
Both single-interval timing tasks (Var, Fix; Fig. 1 A and B)
demonstrated significant deficits in the patients compared with
the control group. The larger difference in thresholds was found
for the reference interval having a variable duration (significant at
the level of P < 0.001, t test on log-transformed data; effect size
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0.87; Fig. 2A). The difference for a reference of fixed duration
was also significant, with a smaller effect size (significant at the
level of P < 0.05, t test on log-transformed data; effect size 0.40;
Fig. 2A). In accordance with the group-level analysis, single-
subject inference based on z scores demonstrated a frequency of
occurrence of significant impairments with P < 0.05 in 44% of
the patients for the timing of single intervals with variable ref-
erence duration and 29% for fixed-reference duration (Fig. 2B).
The relative timing of beat-based rhythmic patterns was sys-
tematically assessed at three levels of perceptual analysis: the
detection of a regular beat (Fig. 1C, Reg), the detection of a de-
viation from an isochronous beat (Fig. 1D, Iso), and the detection
of a distortion in a metrical beat pattern (Fig. 1E, Met). No group
level deficit in performance was found for any of the three tasks
(not significant at the level of P < 0.05; Reg, Mann–Whitney
U test; Iso, Welch’s t test; Met, Mann–Whitney U test; Fig. 2A).
The frequency of occurrence of individual deficits was low overall
and comparable to that in controls: Significant impairments for
the detection of a roughly regular beat, the deviation from an
isochronous beat, and the distortion in a metrical beat were found
in 9%, 6% and 12%, respectively (Fig. 2B).
No correlations were found between performance in perceptual
timing tasks and the duration or severity of motor symptoms (Fig.
S2 and Table S1). Impairments tended not to occur in pre-
symptomatic individuals, and were substantial in some severely
affected individuals, but there was no consistent relationship at
the group level.
Discussion
This work tested the role of the human cerebellum as a critical
substrate for the perceptual timing of single intervals based on
their absolute duration and that of rhythmic sequences with
Author contributions: M.G. and T.D.G. designed research; M.G., F.E.C., and P.F.C. per-
formed research; M.G. and F.E.C. analyzed data; and M.G., F.E.C., P.F.C., and T.D.G. wrote
the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission. W.T.T. is a guest editor invited by the Editorial
Board.
Freely available online through the PNAS open access option.
1
To whom correspondence should be addressed. E-mail: manon.grube@ncl.ac.uk.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.
1073/pnas.0910473107/-/DCSupplemental.
PNAS Early Edition | 1 of 5

Fig. 1. Stimuli for the five timing tasks depicting one example of one target
stimulus (black) and one reference stimulus (gray) per task. Horizontal lines
depict tones (200 Hz; 100 ms); ticks represent units corresponding to an
underlying beat; dotted lines mark interval changes in target stimuli.
(A) (Var) Variable-single interval discrimination. (B) (Fix) Fixed-single interval
discrimination. (C) (Reg) Regularity detection. (D) (Iso) Isochrony-deviation
detection. (E) (Met) Metrical pattern discrimination (roving of unit-duration
omitted for clarity; thick ticks marking the metrical beat of 4).
a regular beat based on the relative durations of intervals. The
findings are based on reliable measures of individual perfor-
mance for both types of timing in a large and homogeneous
group of patients with a specific type of cerebellar degeneration
(SCA-6). A significant deficit in the patients compared with the
matched control group was demonstrated for the timing of single
intervals, but not for rhythmic sequences based on a regular beat.
The data suggest impairment in a mechanism for absolute timing
and preservation of mechanisms of relative timing.
Deficit in Absolute Duration-Based Timing. The significant deficit in
the timing of single intervals in the patients compared with con-
trols is consistent with previous neuropsychological reports of
deficits or trends to deficits in related tasks (16, 17, 22, 23). Some
inconsistency of the effect in previous studies may reflect the
heterogeneity of lesions in these populations of stroke patients (14,
15). The current study assessed 34 individuals with a genetically
determined, isolated disorder of the cerebellum that advances in
a stereotyped way from the superior to the inferior part (24).
Fig. 2. Timing thresholds group data and frequency of occurrence of in-
dividual deficits for patients (n = 34; black) compared with controls (n = 40;
gray). (A) Mean timing thresholds and SEMs. Group differences were sig-
nificant for Var and Fix. (B) Proportion of significant impairment at the in-
dividual level Note high values for Var and Fix, contrasted by low values for
Reg, Iso, and Met. Significance level was P < 0.05.
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Subjects were recruited on the basis of their diagnosis with SCA-6
and included irrespective of the severity of motor symptoms.
Substantial group effects were shown despite the inclusion of
asymptomatic subjects. The absence of correlations with motor
symptoms may be due to insufficient power or dissociation of
neural substrates for motor tasks relevant to ataxia and perception
within the cerebellum. The group-level and individual deficits for
the fixed-interval task, where the reference interval is presented
repeatedly throughout the test, compare well with the moderate
effects reported in previous studies (4, 14, 16). The larger effect
size and proportion of individual deficits in more than 40% of the
patients in the variable-interval task, in which the duration of
the reference interval changes from trial to trial, support the
specific involvement of the cerebellum in the perceptual analysis of
unrepeated intervals. In this task, the duration of each interval
must be timed anew with no possibility of creating an internal long-
term reference: The task is a more exacting test of the perception
of absolute time. Cerebellar integrity seems crucial to the normal
functioning of this stopwatch-like timing mechanism (25). This
notion is consistent with cerebellar activation in normal individuals
being stronger for the perception of novel compared with familiar
sequences of intervals (11).
One alternative explanation for the difference in performance
between patients and controls could be based on cognitive
demands and the recent implication of the cerebellum in cog-
nition (26–29). This appears unlikely, as the single-interval tim-
ing tasks are less demanding than those of beat-based timing,
and as the cognitive deficits demonstrated in patients with cer-
ebellar damage were specific to aspects of executive function or
attention (27–29) and would not lead to the present dissociation.
The cerebellar substrate for interval perception might have a
number of precise anatomical locations. Previous functional
imaging studies have not demonstrated clear differences between
cerebellar activation patterns for absolute and relative percep-
tual timing (7, 8, 10, 11, 30). Repetitive transcranial magnetic
stimulation targeting the medial and right cerebellum can pro-
duce similar acute deficits in absolute time-interval perception
(31), demonstrating consistent effects of both chronic and acute
cerebellar dysfunction. One previous neuropsychological report
of a perceptual timing deficit implicated superior parts of the
cerebellum, in particular, the right lateral hemisphere (14). The
present study demonstrates a specific deficit in absolute time
perception in a group with SCA-6 that experiences stereotyped
progression of the cerebellar degeneration from the superior to
the inferior parts, especially affecting the vermis (24). Our data
are consistent with previous suggestions of a particular role of
the superior cerebellum in absolute timing, and suggest a par-
ticular importance of the midline cerebellum.
Preservation of Relative, Beat-Based Timing Mechanisms. All three
tests of relative timing of rhythmic sequences based on a regular
beat were unaffected in the patients at the group level. The first
task, requiring the detection of regularity, was based on iso-
chronous sequences that become increasingly irregular (19) and
was unaffected with the exception of a few individuals. If the de-
tection of a regular beat depended on accurate single-interval
timing in a hierarchical fashion, one would expect to find a deficit
in the regularity task also. The lack of impairment suggests that this
task depends on a mechanism distinct from the stopwatch-type
device that we suggest for single intervals. The second task, the
detection of a deviation from an isochronous beat, was also un-
impaired at the group level. Thresholds were lower than those for
single intervals or within sequences with no regular beat, as
reported in previous studies (20, 32, 33), with the drop in thresh-
olds being even larger in the patients than in the controls. The third
task, assessing the ability of subjects to use metrical sequences to
achieve greater precision in rhythmic timing tasks (21), was also
unimpaired at the group level.
Grube et al.
 All three tasks could be accomplished by one or more mech-
anisms that are different from the timing of single intervals.
Unlike single-interval mechanisms being based on absolute du-
ration, those additional mechanisms would use the presence of
a regular beat as an alternative reference frame for the timing of
intervals relative to the beat. Psychophysical data from previous
studies in normals support a dissociation between mechanisms for
duration-based as opposed to beat-based timing of intervals and
rhythmic sequences (20, 21, 32, 34–38). The preservation of rela-
tive timing tasks is not consistent with the idea that the cerebellum
provides a single mechanism subserving both single-interval and
beat-based timing; rather, the data suggest one or more mecha-
nisms of perceptual entrainment with a regular beat that are
independent of single-interval timing and can occur despite cere-
bellar damage. The preservation of beat-based perception here is
consistent with that of sensorimotor transduction elsewhere (39),
and with a perceptual mechanism of entrainment that depends on
a neural substrate that is unaffected in the present study.
We cannot rule out the possibility that focal lesions in parts of
the cerebellum that were unaffected in the patients in the present
study might impair beat-based rhythm perception. The present
study demonstrates an obligatory role of the cerebellum in abso-
lute, subsecond timing but does not exclude any possible role in
relative timing involving mechanisms that are relatively spared by
present data further suggest that beat-based perceptual timing
can function independently of an impairment in this mechanism;
they do not allow a direct inference on a common mechanism of
entrainment for motor and perceptual timing.
The occurrence of impairment may relate to views of the
cerebellum as a “universal” basic sensory acquisition controller
(1) and as a part of a network for processing magnitude (55), in
this case time or duration. Both views are congruent with the
present argument for a cerebellar role in the absolute, duration-
based perceptual timing of single intervals but not to the relative,
beat-based timing within rhythmic sequences. The involvement
of the postulated cerebellar mechanism of absolute, subsecond
timing in other perceptual modalities is supported by previous
reports of the effect of cerebellar TMS on duration-based so-
matosensory timing (56) and cerebellar activations in visual
timing (7, 11).
Studies of lesions of the other components, including the basal
ganglia and prefrontal cortex, and in other modalities will allow
further tests of the dissociation between duration-based and
beat-based timing.
Materials and Methods

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Subjects. The patient group included 34 individuals (12 males) with geneti-
the degenerative process. We would point out, however, that the cally diagnosed spinocerebellar ataxia type 6 (SCA-6) (Fig. 3).The patients’
study includes subjects with advanced disease and widespread at- age range was 45–81 y (mean 64 ± 10 SD); estimated premorbid IQs (57) and
rophy who do not show individual deficits in beat-based rhythm verbal IQs (58) were in the normal range (premorbid, mean 101 ± 7 SD;
perception. The preservation of performance contrasts with verbal, mean 105 ±11 SD). Duration of symptoms was self-reported and
expectations based on cerebellar activation in fMRI studies of ranged from 0 to 20 y (mean 8.8 ± 5.8 SD), severity of motor impairment
normal controls, and suggests that such activity might not be an assessed on a locally developed scale from 1 to 5; patient details are listed in
obligatory aspect of relative time perception (9, 11, 13, 40). Table S2. SCA-6 is an autosomal-dominant disease caused by a loss-of-
function mutation in a voltage-gated calcium channel that specifically
Cerebellar Contribution to the Timing Network of the Brain. This affects the Purkinje cells of the cerebellum. Degeneration starts at the su-
work suggests a differential involvement of the cerebellum as perior–anterior end and progresses inferior–posteriorly in a stereotyped
a part of the perceptual timing network of the brain. A “cere- manner (24). The matched control group included 40 subjects (18 males) of
bellar clock” has previously been promoted as a device that both 45–81 y (mean 64 ± 9 y). There were no group differences in age, years of
measures absolute interval duration and entrains with a regular education, estimated premorbid IQ, or hearing sensitivity (Table 1).
beat of a sequence of intervals at the subsecond level (20, 41–43).
The present data support a role of the cerebellum in the former
but not the latter. We argue for a role for the cerebellum as
a stopwatch mechanism with specific and obligatory involvement
in absolute time-interval perception (25), in which the cerebellar
circuitry would provide the suitable neural machinery (44–46).
This is in accordance with the notion of “event timing” and the
multiple-timer model suggested by Ivry et al. (20, 42, 43).
The preserved beat-based perception suggests a distinct neural
substrate from the proposed cerebellar stopwatch mechanism for
single-interval timing. Possible substrates include a distinct cere-
bellar subregion. However, the preservation of beat-based per-
ception even in patients with extensive cerebellar damage would
argue against this. Alternatively, beat-based perception may de-
pend on distinct parts of the timing network beyond the cere-
bellum such as the basal ganglia or cerebral cortex (10, 30, 47, 48).
Anatomical connections between the cerebellum and the basal
ganglia and prefrontal cortex (via the thalamus) (46, 49–51) could
support efficient integrated network processing. Recent func-
tional data further suggest specialized loops or zones of cortico-
cerebellar connectivity, including one for sensori-motor functions
involving cerebellar lobules V–VII (52, 53).
This study addresses mechanisms of perceptual timing, and any
link between perceptual and motor timing (54) needs to be made
with caution. Previous patient studies suggested an obligatory
cerebellar role in the motor timing of individual movements in
isolation and in the context of a regular beat (4, 14, 18). Deficits in
perceptual timing were here only demonstrated for single inter- Fig. 3. Structural MRI scans of SCA-6–induced cerebellar degeneration in
vals in isolation and not within the context of a regular beat. four patients. (A) P27: male, 60 y, 3 y postonset, x 4. (B) P32: female, 62 y, 6 y
Overall the data could support a common cerebellar mechanism postonset, x +4. (C) P07: female, 69 y, 10 y postonset, x −7. (D) P13: male,
in the timing of individual motor or perceptual events. The 74 y, 20 y postonset, x −3. x coordinates according to MNI convention.

Grube et al. PNAS Early Edition | 3 of 5

 Table 1. Control and patient group descriptive statistics
Age, y Education, y
Controls 64.1 ± 9.0 10.0 ± 3.0*
Patients 64.1 ± 10.1 11.0 ± 1.4*
Difference NS NS
Values are group mean ± SD in cases of normal distributions, and group medians ± mean deviations from the
median for non-normal distributions (*tested by Lilliefors modification of the Kolmogorov–Smirnoff test for
composite normality, significance level, P = 0.05). No significant group differences were found at the level of P <
0.05, tested by the independent two-sample t test or Mann–Whitney U test in cases of normal and non-normal
distributions, respectively. IQ, intelligence quotient; NS, not significant.
Setup and Stimuli. All stimuli were composed of 200-Hz pure tones, 100 ms in
duration with 20 ms gating times. Stimuli were created using Matlab 6.5
(Mathworks) with a 44.1-kHz sampling rate and 16-bit resolution, delivered at
70 dB rms Sound Pressure Level via an external soundcard (Edirol Audio Capture
UA-3FX) and closed headphones (Sennheiser HD265 linear).
Procedure. The timing tasks included two interval timing tasks and three beat-
based timing tasks. All tasks used an adaptive, two alternative forced-choice
procedure following a two-down–one-up tracking algorithm (59) (Fig. S1).
Each test consisted of 60 trials, preceded by a minimum of three practice
trials to familiarize the subject with the task. Each trial contained one target
and one reference stimulus in randomized order, and the task of the subject
was to indicate the position of the target. Target positions were randomized
at equal probabilities, with order fixed across subject. Interstimulus and in-
tertrial intervals were 1,500 ms each. Subjects communicated their responses
by pressing corresponding buttons on a response box (controls) or pointing
to corresponding circles on paper (patients) to avoid motor difficulties with
button presses. Response time was not limited, but subjects were encour-
aged to make the decisions quickly. The difference between target and
reference was at suprathreshold levels initially and decreased after two
responses correct in a row and increased after each incorrect one. A larger
step size was used up to the fourth reversal (change between increase and
decrease) and after that a smaller one. Thresholds were calculated as the
mean of the last six reversals, estimating the 70.7% correct point of the
psychometric function (59). The total time needed was less than 2 h, in-
cluding a pure tone audiogram for 0.125, 0.25, 0.5, 1, 2, and 4 kHz.
Tasks of Absolute Timing of Single Intervals. Variable interval timing (Var). In the
variable interval task, subjects were required to discriminate a longer target
interval against a shorter reference interval (Fig. 1A). Intervals were marked
by pairs of tones; the reference interval had a variable interonset-interval of
300, 360, 420, 480, 560, or 600 ms in duration (at equal probabilities in
pseudorandomized order fixed across subjects). The target interval had
a silent gap between the flanking tones that was longer than the reference
by 90% of the silent reference interval initially and adaptively adjusted in
steps of 12% and 6%.
Fixed-interval timing (Fix). As in the variable-interval task, subjects were re-
quired to discriminate a longer target against a shorter reference interval,
with the only difference that the interonset-interval of the reference was
fixed at 300 ms in this task (Fig. 1B). The target interval was longer by 30%
initially and adaptively adjusted in steps of 4% and 1.33%.
Tasks of Relative Timing of Beat-Based Patterns. Regular beat detection (Reg). In
the beat detection task, subjects had to discriminate a more regular target
sequence against a less regular reference sequence based on an underlying
beat and despite the introduction of an increasing amount of irregularity
(Fig. 1C). Both sequences consisted of 11 tones and were based on a regular
beat of a 400 ms interonset-interval. The beat could easily be detected in the
target sequence initially as it was perfectly regular (isochronous). The ref-
erence sequence was highly irregular as each time interval was shortened or
lengthened at random by 30% on average, making the underlying regular
beat imperceptible (19). The mean irregularity in the target, starting at 0%
initially, was adaptively increased in steps of 4% and 2.5% until the un-
derlying beat could not be detected and the target could not be reliably
discriminated against the reference anymore.
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Estimated premorbid IQ Audiogram, dB hearing loss
103.0 ± 9.7* 19.4 ± 11.0
102.0 ± 4.9* 20.6 ± 7.9
NS NS
Isochrony deviation detection (Iso). Subjects were required to detect a length-
ening of the third interval in an otherwise isochronous, five-tone sequence
with a regular interonset-interval of 300 ms (20) (Fig. 1D). This task was
physically identical to that using a fixed single interval (B, Fix), with the
added context of an isochronous beat. The initial difference in interval
length was 20%; adaptive step sizes were 2% and 1%.
Metrical pattern discrimination (Met). Subjects were required to detect a relative
change in the timing of a rhythmic sequence of seven tones with a metrical
beat (Fig. 1E) based on two levels of periodicity (21). The duration of the
lower level periodicity was 200 ms on average (roved from 180 to 220 ms in
4-ms steps). The higher-level metrical beat of 4 was induced by a regular
occurrence of temporally induced accents on every fourth unit (with a peri-
odicity of 800 ms on average; marked by thick ticks). The target contained
a change in the relative timing of the intervals within the sequence that
resulted in a distortion of the metrical beat pattern. The change in pattern
was introduced by changes in duration in the four long intervals of 2x one
and 2x two silent units, where one of each was lengthened and one short-
ened, all by the same percentage. The intervals containing silent units were
thus no longer integer multiples of the underlying unit and the pattern
would sound “wrong.” The change amounted to 65% initially, and was
adaptively adjusted in steps of 12% and 6%.
Statistical Data Analysis. Group-level comparison. Distribution of data samples
was tested by the Lilliefors modification of the Kolmogorov–Smirnoff test for
composite normality. Between-group comparisons were carried out by Stu-
dent’s or Welch’s t test for normally distributed samples (original or logged)
with equal or unequal variance, or the Mann–Whitney U Test for non-
normally distributed samples of equal dispersion (no unequal dispersion
occurred). The significance level was P = 0.05. Effect sizes were calculated
taking into account sample size.
Single-subject inference. Single-subject inference was based on z score trans-
formation of patients’ thresholds in relation to the control group while taking
into account the effect of age. A complete list of age-dependency correlation
coefficients based on the use of Pearson product-moment or Spearman rank
correlation test for normal and nonnormal distributions, respectively, is given
in Table S2.
Age-dependence of thresholds was modeled by linear regression of the
control data:
x ¼ β1 · age þ β0 þ ε
where x is the individual threshold, β1 and β0 are the regression coefficients,
and ε is the error of the regression model between threshold and age.
Individual patients’ z scores were calculated as a function of age:
_
zðageÞ ¼ ðθ − x ðageÞÞ=stdðεÞ
where θ is the individual threshold, bx ðageÞ is the age-dependent expected
threshold, and std(ε) is the SD of the error of the regression model.
The significance level was P = 0.05, equivalent to a score of z > 1.65.
ACKNOWLEDGMENTS. We thank Sukhbinder Kumar and Martin O’Gorman
for advice with data analysis and Sundeep Teki for comments on the man-
uscript. This work was supported by Wellcome Trust Grant WT061136MA (to
T.D.G.). F.C. is funded by an Ataxia UK Ph.D. studentship. P.F.C. and T.D.G.
are both Wellcome Trust Senior Fellows in Clinical Science.
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